Persons in the US with end stage renal disease (ESRD) have an annual mortality rate of over 20% and an age-specific death rate from cardiovascular disease that is 10-100 times higher than the general population. Much of this excess mortality is due to sudden cardiac death (SCD). Surprisingly, few prospective studies have examined risk factors for SCD in ESRD patients and these studies did not measure many risk factors known to be important in the general population. In the CHOICE cohort study, we found an SCD incidence of 18% over 4 years of follow up. Our overall hypothesis is that factors that increase risk for SCD in the general population are highly prevalent in the dialysis population and are independent predictors of altered autonomic tone, impaired ventricular conduction, and SCD. We propose a prospective, longitudinal study of 1,000 incident ESRD patients treated with hemodialysis to determine the cardiovascular, dialysis-related, and genetic risk factors leading to altered autonomic tone, impaired ventricular conduction, and SCD. Participants aged 18 and older will be recruited from the Baltimore area. We anticipate that 60% of the cohort will be African American and 50% will have diabetes. Techniques developed in other successful studies of ESRD by the investigative team will be used to recruit and follow participants. Coronary calcium, vessel stenosis, and left ventricular structure and function will be assessed using computed tomography (CT) and CT angiography at baseline; ECGs, questionnaires and biological specimens will be collected at baseline and annually. Heart rate variability, measures of QT duration, and presence of ventricular late potentials will be assessed by analysis of annual ECG recordings. Cause of death will be adjudicated using standard criteria. This study will also allow identification of dialysis-related risk factors for SCD and its intermediates that are unique to ESRD, setting the stage for clinical trials to test therapies to prevent SCD in this high risk population. In addition, the proposed work will provide an infrastructure to answer, in future studies, a host of questions related to the pathogenesis of morbidity and mortality in the ESRD population. [unreadable] [unreadable] [unreadable] [unreadable]